Approximately 25% of the products being developed by the biotechnology industry are antibodies and many of these antibodies are directed to epitopes on human cells and tissues. We are proposing a novel concept for the production of antibodies with therapeutic potential that is based on recent advances in protein-protein interactions and recent developments in transgenic technology. Execution of this concept will obviate many of the expensive and time consuming modifications that are frequently required after potentially therapeutic monoclonal antibodies are identified in order to optimize their pharmacological properties and to make them amenable to large scale production. By combining recent data derived from in vitro studies with the nascent understanding of genomics, we will extend the range of epitopes that can be accessed and, therefore, extend the range of potentially therapeutic antibodies. PUBLIC HEALTH RELEVANCE: During the past 15 years, more than 20 therapeutic antibodies have been developed to treat human disease, particularly in the fields of autoimmunity and cancer. We have proposed a novel method to obtain potentially therapeutic antibodies that will recognize targets that cannot be obtained from conventional sources. In addition, the technology will engineer antibodies that have improved pharmacological attributes and better manufacturing properties. This technology will provide a cost-effective route to increasing the range of therapeutic candidates for the treatment of human disease.